Syntheses of COX-2 Inhibitors

Celecoxib is prepared in a convergent synthesis by a classical condensation reaction, which gives a pyrazole from the corresponding 1,3-diketone and a hydrazine. [205] The hydrazine is obtained from aniline by sulfonation, diazotisa-tion and reduction. The 1,3-diketone is accessible in one step from 4-methylac-etophenone and ethyl trifluoroacetate. 

Rofecoxib is also accessible by a comparatively short synthesis. [206] The starting material, methyl phenyl sulfide, is converted by Friedel-Crafts acylation and oxidation into the required sulfonylacetophenone. This is brominated and finally condensed with phenylacetic acid to result in the active compound. 

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